Effects of Adjunctive Treatment with Combined Cytokines in a Neutropenic Mouse Model of Multidrug‐Resistant Enterococcus faecalis Septicemia

Abstract

This study suggests that adjunctive application of combined cytokines may not be more beneficial than only G-CSF in combination with an antibiotic to treat multidrug-resistant enterococcal infection.

Effect of adjunctive treatment with gamma interferon against Pseudomonas aeruginosa pneumonia in neutropenic and non-neutropenic hosts

“…Previous studies in our laboratory and elsewhere have shown that cytokine effect against bacterial infections is influenced by the level of infectious burden [7,9,[23][24][25]. The MLD (LD 100 ) of PSA used in the present study could be overwhelming for the hosts coupled with the virulence characteristics of PSA in acute infection [4].…”

“…The major findings in this study were that interferon gamma had no benefit on its own and that a combination of IFN-␥ as an adjunct to ceftazidime resulted in no improvement in therapy of PSA pneumonia in both immunocompromised and immunocompetent hosts after onset of infection. A few studies on have shown beneficial effect of IFN-␥ in enhancing antibiotic therapy in animal infection models [7,9,22]. The study by Onyeji et al [9] showed adjunctive efficacy of IFN-␥ when combined with gentamicin and vancomycin in the treatment of GVRE in non-neutropenic (NN) mice but not in neutropenic mice.…”

“…Adjunctive immunomodulatory therapies in the management of infections are a growing area of interest because potentiation of the non-specific immune system offers an opportunity to maximise resolution of serious infections [7].…”

“…Studies on an immunotherapeutic approach involving the use of interferon-gamma (IFN-␥) against gentamicin-and vancomycin-resistant Enterococcus faecalis (GVRE) have been investigated in our laboratory [7][8][9]. In these studies, IFN-␥ significantly augmented the antienterococcal activities of gentamicin and vancomycin in vitro as well as in vivo in the non-neutropenic (NN) mouse model.…”

“…As a result of the promising adjunctive IFN-␥ treatment, we hypothesised that IFN-␥ could be a beneficial adjunct in the treatment of PSA pneumonia infections. Although there are several reports on merits and demerits of both endogenous IFN-␥ and administered IFN-␥ in infection models [14][15][16][17][18][19], administration of IFN-␥ and several other immunomodulators in combination with antimicrobial therapy has undergone limited study [7][8][9] and no data are available concerning combined IFN-␥ and antibiotic in the treatment of acute PSA pneumonia. Thus, the purpose of this study was to evaluate the effects of administration of IFN-␥ in combination with ceftazidime (TAZ) in the treatment of a mouse model of pneumonia induced by PSA in both neutropenic (NT) and non-neutropenic (NN) hosts after onset of infection.…”